Medical Specialties Commons^™

Ryanodine Receptor 1-Related Disorders: An Historical Perspective And Proposal For A Unified Nomenclature, Tokunbor A Lawal, Joshua J Todd, Jessica W Witherspoon, Carsten G Bönnemann, James J Dowling, Susan L Hamilton, Katherine G Meilleur, Robert T Dirksen

Faculty, Staff and Students Publications

The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 and RYR1 variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then, RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. RYR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically, RYR1-RM-affected individuals were …

Lung Nodule In A Patient With Multiple Myeloma, William C Harding, Mathieu Marcoux, Roberto F Casal, Lara Bashoura, John Stewart, Hans C Lee, Saadia A Faiz

Faculty, Staff and Student Publications

No abstract provided.

Structural Basis Of Ion Transport And Inhibition In Ferroportin, Yaping Pan, Zhenning Ren, Shuai Gao, Jiemin Shen, Lie Wang, Zhichun Xu, Ye Yu, Preetham Bachina, Hanzhi Zhang, Xiao Fan, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron deficiency anemia. Here we present the structures of the ferroportin from the primate Philippine tarsier (TsFpn) in the presence and absence of hepcidin solved by cryo-electron microscopy. TsFpn is composed of two domains resembling a clamshell and the structure defines two metal ion binding sites, one in each domain. Both structures are in an outward-facing conformation, and …

Young Versus Aged Microbiota Transplants To Germ-Free Mice: Increased Short-Chain Fatty Acids And Improved Cognitive Performance, Juneyoung Lee, Venugopal R Venna, David J Durgan, Huanan Shi, Jacob Hudobenko, Nagireddy Putluri, Joseph Petrosino, Louise D Mccullough, Robert M Bryan

Faculty, Staff and Students Publications

Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline. Fecal transplant gavages (FTGs) from aged (18–20 months) or young (2–3 months) male C57BL/6 mice into germ-free male C57BL/6 mice (N = 11 per group) were initiated at ~3 months of age. Fecal samples were collected and behavioral testing was performed over the study period. Bacterial community …

Loss Of Class Iii Phosphoinositide 3-Kinase Vps34 Results In Cone Degeneration, Ammaji Rajala, Feng He, Robert E Anderson, Theodore G Wensel, Raju V S Rajala

Faculty, Staff and Students Publications

The major pathway for the production of the low-abundance membrane lipid phosphatidylinositol 3-phosphate (PI(3)P) synthesis is catalyzed by class III phosphoinositide 3-kinase (PI3K) Vps34. The absence of Vps34 was previously found to disrupt autophagy and other membrane-trafficking pathways in some sensory neurons, but the roles of phosphatidylinositol 3-phosphate and Vps34 in cone photoreceptor cells have not previously been explored. We found that the deletion of Vps34 in neighboring rods in mouse retina did not disrupt cone function up to 8 weeks after birth, despite diminished rod function. Immunoblotting and lipid analysis of cones isolated from the cone-dominant retinas of the …

Zmat3 Is A Key Splicing Regulator In The P53 Tumor Suppression Program, Kathryn T Bieging-Rolett, Alyssa M Kaiser, David W Morgens, Anthony M Boutelle, Jose A Seoane, Eric L Van Nostrand, Changyu Zhu, Shauna L Houlihan, Stephano S Mello, Brian A Yee, Jacob Mcclendon, Sarah E Pierce, Ian P Winters, Mengxiong Wang, Andrew J Connolly, Scott W Lowe, Christina Curtis, Gene W Yeo, Monte M Winslow, Michael C Bassik, Laura D Attardi

Faculty, Staff and Students Publications

Although TP53 is the most commonly mutated gene in human cancers, the p53-dependent transcriptional programs mediating tumor suppression remain incompletely understood. Here, to uncover critical components downstream of p53 in tumor suppression, we perform unbiased RNAi and CRISPR-Cas9-based genetic screens in vivo. These screens converge upon the p53-inducible gene Zmat3, encoding an RNA-binding protein, and we demonstrate that ZMAT3 is an important tumor suppressor downstream of p53 in mouse Kras

Allogeneic Mesenchymal Cell Therapy In Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The Cctrn Seneca Trial, Roberto Bolli, Emerson C Perin, James T Willerson, Phillip C Yang, Jay H Traverse, Timothy D Henry, Carl J Pepine, Raul D Mitrani, Joshua M Hare, Michael P Murphy, Keith L March, Sohail Ikram, David P Lee, Connor O'Brien, Jean-Bernard Durand, Kathy Miller, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Adrian P Gee, Sara Richman, Doris A Taylor, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara M Simpson, Dejian Lai, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari

Faculty, Staff and Student Publications

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment.

OBJECTIVES: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC.

METHODS: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10

RESULTS: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the …

Improving Therapeutic Potential Of Non-Viral Minimized Dna Vectors, Lirio M Arévalo-Soliz, Cinnamon L Hardee, Jonathan M Fogg, Nathan R Corman, Cameron Noorbakhsh, Lynn Zechiedrich

Faculty, Staff and Students Publications

The tragic deaths of three patients in a recent AAV-based X-linked myotubular myopathy clinical trial highlight once again the pressing need for safe and reliable gene delivery vectors. Non-viral minimized DNA vectors offer one possible way to meet this need. Recent pre-clinical results with minimized DNA vectors have yielded promising outcomes in cancer therapy, stem cell therapy, stem cell reprograming, and other uses. Broad clinical use of these vectors, however, remains to be realized. Further advances in vector design and production are ongoing. An intriguing and promising potential development results from manipulation of the specific shape of non-viral minimized DNA …

Modeling Age-Dependent Developmental Changes In The Expression Of Genes Involved In Citrulline Synthesis Using Pig Enteroids, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Douglas G Burrin, Juan C Marini

Children’s Nutrition Research Center Staff Publications

metabolism of citrulline and arginine are well characterized. Enteroids, a novel ex-vivo model that recreates the three-dimensional structure of the intestinal crypt-villus unit, have shown to replicate molecular and physiological profiles of the intestinal segment from where they originated ("location memory").

Objective: The present study tested the hypothesis that enteroids recapitulate the developmental changes observed in vivo regarding citrulline production in pigs ("developmental memory").

Methods: Preterm (10- and 5-d preterm) and term pigs at birth, together with 7- and 35-d-old pigs were studied. Gene expression was measured in jejunal samples and in enteroids derived from this segment. Whole body citrulline …

Type 1 Doing Well: Pilot Feasibility And Acceptability Study Of A Strengths-Based Mhealth App For Parents Of Adolescents With Type 1 Diabetes, Marisa E Hilliard, Viena T Cao, Sahar S Eshtehardi, Charles G Minard, Rana Saber, Debbe Thompson, Lefkothea P Karaviti, Barbara J Anderson

Children’s Nutrition Research Center Staff Publications

Background: We evaluated the feasibility and acceptability of a pilot behavioral intervention delivered to parents of adolescents with type 1 diabetes (T1D) via mobile-friendly web app. The Type 1 Doing Well app aimed to promote supportive family diabetes management by helping parents recognize and reinforce teens' positive diabetes-related behaviors ("strengths").

Methods: Parents (n = 80, 74% recruitment) of adolescents (age range = 12-17 years, M = 15.3 ± 1.5 years, 59% female, 56% insulin pump, M hemoglobin A1c (HbA1c) = 9.0% ± 2.1%) were randomized 2:1 to intervention or control (i.e., usual medical care with or without app) for …

Β-Cell Impairment And Clinically Meaningful Alterations In Glycemia In Obese Youth Across The Glucose Tolerance Spectrum, Joon Young Kim, Hala Tfayli, Fida Bacha, Sojung Lee, Nour Gebara, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background/aims: In obese youth, it is not clear what degree of β-cell impairment translates to glucose dysregulation commensurate with shifts from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes. We aimed to investigate the quantitative relationship between β-cell (clamp-measured disposition index [DI]) and OGTT glucose area under the curve (G-AUC) in obese youth across the spectrum of glucose tolerance.

Methods: Data from 152 youth (58 African-American [AA] and 94 American-White [AW]; 73 NGT, 48 IGT, and 31 type 2 diabetes) who completed a 3-h hyperinsulinemic (80 mu/m2/min)-euglycemic clamp, and a 2-h hyperglycemic (225 mg/dL) clamp …

Prenatal Depression And Risk Of Short Interpregnancy Interval In A Predominantly Puerto Rican Population, Sami Backley, Alex Knee, Penelope Pekow, Glenn Markenson, Katharine O White, Corina Schoen, Lisa Chasan-Taber

Faculty, Staff and Student Publications

Background: Short interpregnancy interval (IPI) is associated with risk of adverse pregnancy outcomes; however, few studies have evaluated the role of depression as a risk factor for short IPI. Puerto Rican women in the United States experience disparities in adverse birth outcomes and have the highest birth rates.

Methods: We analyzed the association between prenatal depressive symptoms and IPI in Proyecto Buena Salud, a prospective cohort of predominantly Puerto Rican women in Western Massachusetts (2006–2011). Depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) in early, mid, and late pregnancy. We calculated follow-up time as the difference between the …

Aerosol Generation With Common Rhinologic Devices: Cadaveric Study Conducted In A Surgical Suite, Bailey Leconte, Garren M I Low, Martin J Citardi, William C Yao, Arturo A Eguia, Amber U Luong

Faculty, Staff and Student Publications

No abstract provided.

Variable Expression Of Msh6 In Endometrial Carcinomas With Intact Mismatch Repair And With Mlh1 Loss Due To Mlh1 Methylation, Nidhi Tandon, Courtney Hudgens, Bryan Fellman, Michael T Tetzlaff, Russell R Broaddus

Faculty, Staff and Student Publications

Immunohistochemistry for mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 is an effective screen to detect individuals at risk for Lynch syndrome. College of American Pathologists guidelines stipulate that protein expression should be reported as present versus absent, as most patients with germline mutations in a mismatch repair gene have complete loss of protein expression in tumor cells. A similar approach is employed to screen for cancer patients eligible for immune checkpoint blockade. This "all or none" interpretive approach ignores substantial evidence that mismatch repair may be more finely regulated by other mechanisms. We have observed clinically that MSH6 expression …

Identification Of Novel Candidate Risk Genes For Myelomeningocele Within The Glucose Homeostasis/Oxidative Stress And Folate/One-Carbon Metabolism Networks, Paul Hillman, Craig Baker, Luke Hebert, Michael Brown, James Hixson, Allison Ashley-Koch, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) are the second most common complex birth defect, yet, our understanding of the genetic contribution to their development remains incomplete. Two environmental factors associated with NTDs are Folate and One Carbon Metabolism (FOCM) and Glucose Homeostasis and Oxidative Stress (GHOS). Utilizing next-generation sequencing of a large patient cohort, we identify novel candidate genes in these two networks to provide insights into NTD mechanisms.

METHODS: Exome sequencing (ES) was performed in 511 patients, born with myelomeningocele, divided between European American and Mexican American ethnicities. Healthy control data from the Genome Aggregation database were ethnically matched and …

Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute

Faculty, Staff and Students Publications

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in …

Donor And Transplant Candidate Selection For Solid Organ Transplantation During The Covid-19 Pandemic, N Thao N Galvan, Nicolas F Moreno, Jay E Garza, Susan Bourgeois, Marion Hemmersbach-Miller, Bhamidipati Murthy, Katherine Timmins, Christine A O'Mahony, James Anton, Andrew Civitello, Puneet Garcha, Gabe Loor, Kenneth Liao, Alexis Shaffi, John Vierling, Rise Stribling, Abbas Rana, John A Goss

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating …

Chronic Ulcers And Malnutrition In An African Patient\, Timothy G Singer, Monica A Bray, Audrey Chan, Saki Ikeda, Brittany Walters, Maren Y Fuller, Carla Falco

Faculty, Staff and Students Publications

An 11-year-old female with a congenitally malformed left hand, sickle-cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared following trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months prior to transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous (IV) antibiotics and close management by a Pediatric Infectious Disease specialist working for a non-governmental organization (NGO) in …

Organizational Readiness Assessment In Acute And Long-Term Care Has Important Implications For Antibiotic Stewardship For Asymptomatic Bacteriuria, Melanie C Goebel, Barbara W Trautner, Yiqun Wang, John N Van, Laura M Dillon, Payal K Patel, Dimitri M Drekonja, Christopher J Graber, Bhavarth S Shukla, Paola Lichtenberger, Christian D Helfrich, Anne Sales, Larissa Grigoryan

Faculty, Staff and Students Publications

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment.

METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale.

RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was …

Pr Depression With Multilead St Elevation And St Depression In Avr By Left Circumflex Artery Occlusion: How To Differentiate From Acute Pericarditis, Zhong-Qun Zhan, Kjell Nikus, Yochai Birnbaum

Faculty, Staff and Students Publications

PR-segment depression with multilead ST-segment elevation and ST-segment depression in lead aVR are classic ECG manifestation of acute pericarditis. We present a patient, where the etiology of these ECG features was acute ST-elevation myocardial infarction due to left circumflex artery occlusion. To avoid misdiagnosis, unnecessary examinations, and inappropriate therapeutic decisions, the possibility of ST-segment elevation myocardial infarction should be kept in mind even when ECG changes typical for pericarditis are encountered in chest pain patients. Findings of QRS widening and QT interval shortening in leads with ST-segment elevation could help to differentiate acute ST-segment elevation myocardial infarction from acute pericarditis.

Outcomes After In Utero Myelomeningocele Repair Based On Delivery Location, Eric P Bergh, Kuojen Tsao, Mary T Austin, Stephen A Fletcher, Suzanne M Lopez, Kenneth J Moise, Anthony Johnson, Ramesha Papanna

Faculty, Staff and Student Publications

Maternal and pediatric delivery outcomes may vary in patients who underwent open fetal myelomeningocele repair and elected to deliver at the fetal center where their fetal intervention was performed versus at the referring physician’s hospital. A prospective cohort study of 88 patients were evaluated following in utero open fetal myelomeningocele repair at a single fetal center between the years 2011–2019. Exclusion criteria included patients that delivered within two weeks of the procedure (n = 6), or if a patient was lost to follow-up (n = 1). Of 82 patients meeting inclusion criteria, 36 (44%) patients were delivered at …

Outcomes After In Utero Myelomeningocele Repair Based On Delivery Location, Eric P Bergh, Kuojen Tsao, Mary T Austin, Stephen A Fletcher, Suzanne M Lopez, Kenneth J Moise, Anthony Johnson, Ramesha Papanna

Faculty, Staff and Student Publications

Maternal and pediatric delivery outcomes may vary in patients who underwent open fetal myelomeningocele repair and elected to deliver at the fetal center where their fetal intervention was performed versus at the referring physician’s hospital. A prospective cohort study of 88 patients were evaluated following in utero open fetal myelomeningocele repair at a single fetal center between the years 2011–2019. Exclusion criteria included patients that delivered within two weeks of the procedure (n = 6), or if a patient was lost to follow-up (n = 1). Of 82 patients meeting inclusion criteria, 36 (44%) patients were delivered at …

Povidone-Iodine Solution As Sars-Cov-2 Prophylaxis For Procedures Of The Upper Aerodigestive Tract A Theoretical Framework, Syed H S Naqvi, Martin J Citardi, Davide Cattano, Luis Ostrosky-Zeichner, Mark I Knackstedt, Ron J Karni

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has raised concerns of inadvertent SARS-CoV-2 transmission to healthcare workers during routine procedures of the aerodigestive tract in asymptomatic COVID-19 patients. Current efforts to mitigate this risk focus on Personal Protective Equipment, including high-efficiency filtration as well as other measures. Because the reservoir for SARS-CoV-2 shedding is in the nasopharynx and nasal and oral cavities, the application of viricidal agents to these surfaces may reduce virus burden. Numerous studies have confirmed that povidone-iodine inactivates many common respiratory viruses, including SARS-CoV-1. Povidone-iodine also has good profile for mucosal tolerance. Thus, we propose a prophylactic treatment protocol for …

Cd123 As A Biomarker In Hematolymphoid Malignancies: Principles Of Detection And Targeted Therapies, Hanadi El Achi, Edouard Dupont, Shilpa Paul, Joseph D Khoury

Faculty, Staff and Student Publications

CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated in leukemic stem cells relative to non-neoplastic hematopoietic stem cells, which makes it a useful diagnostic and therapeutic biomarker in hematologic malignancies. Varying levels of evidence have shown that CD123-targeted therapy represents a promising therapeutic approach in several cancers. Tagraxofusp, an anti-CD123 antibody conjugated to a diphtheria toxin, has been approved for use in patients with blastic …

Association Of Visceral Adipose Tissue And Subclinical Atherosclerosis In Us-Born Mexican Americans But Not First Generation Immigrants, Clarence Gill, Miryoung Lee, Kristina P Vatcheva, Nahid Rianon, Beverly Smulevitz, David D Mcpherson, Joseph B Mccormick, Susan P Fisher-Hoch, Susan T Laing

Faculty, Staff and Student Publications

Background Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT-associated cardiovascular disease risk varies by race, but most studies have been done on Non-Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans. Methods and Results Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual-energy X-ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of …

Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness And Reduce Disease Severity In A Rat Model Of Rheumatoid Arthritis, Mark R Tanner, Redwan Huq, William K A Sikkema, Lizanne G Nilewski, Nejla Yosef, Cody Schmitt, Carlos P Flores-Suarez, Arielle Raugh, Teresina Laragione, Pércio S Gulko, James M Tour, Christine Beeton

Faculty, Staff and Students Publications

Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O2•−) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of …

Tumor Somatic Mutations Also Existing As Germline Polymorphisms May Help To Identify Functional Snps From Genome-Wide Association Studies, Ivan P Gorlov, Xiangjun Xia, Spiridon Tsavachidis, Olga Y Gorlova, Christopher I Amos

Faculty, Staff and Students Publications

We hypothesized that a joint analysis of cancer risk-associated single-nucleotide polymorphism (SNP) and somatic mutations in tumor samples can predict functional and potentially causal SNPs from GWASs. We used mutations reported in the Catalog of Somatic Mutations in Cancer (COSMIC). Confirmed somatic mutations were subdivided into two groups: (1) mutations reported as SNPs, which we call mutational/SNPs and (2) somatic mutations that are not reported as SNPs, which we call mutational/noSNPs. It is generally accepted that the number of times a somatic mutation is reported in COSMIC correlates with its selective advantage to tumors, with more frequently reported mutations being …

Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton

Faculty, Staff and Students Publications

Mutations in the skeletal muscle Ca2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to …

Feasibility And Potential Efficacy Of Commercial Mhealth/Ehealth Tools For Weight Loss In African American Breast Cancer Survivors: Pilot Randomized Controlled Trial, Jeanne M Ferrante, Katie A Devine, Alicja Bator, Ashley Rodgers, Pamela A Ohman-Strickland, Elisa V Bandera, Kevin O Hwang

Faculty, Staff and Student Publications

Weight management after breast cancer (BC) treatment in African American (AA) women is crucial to reduce comorbid conditions and health disparities. We examined feasibility and potential efficacy of commercial eHealth/mHealth tools for weight management in AA BC survivors in New Jersey. Participants (N = 35) were randomized to an intervention (SparkPeople) plus activity tracker, Fitbit Charge (n = 18), or wait-list active control group (Fitbit only, n = 17). Anthropometric, behavioral, and quality of life (QOL) outcomes were collected at baseline, 3, 6, and 12 months. Differences in outcomes were assessed using intent-to-treat analysis. Retention was 97.1%. Both groups lost …

Risk Prediction Rule For Advanced Neoplasia On Screening Colonoscopy For Average-Risk Individuals, Ala I Sharara, Ali El Mokahal, Ali H Harb, Natalia Khalaf, Fayez S Sarkis, Mustapha M El-Halabi, Nabil M Mansour, Ahmad Malli, Robert Habib

Faculty, Staff and Students Publications

BACKGROUND: In resource-limited countries, risk stratification can be used to optimize colorectal cancer screening. Few prospective risk prediction models exist for advanced neoplasia (AN) in true average-risk individuals.

AIM: To create and internally validate a risk prediction model for detection of AN in average-risk individuals.

METHODS: Prospective study of asymptomatic individuals undergoing first screening colonoscopy. Detailed characteristics including diet, exercise and medications were collected. Multivariate logistic regression was used to elucidate risk factors for AN (adenoma ≥1 cm, villous histology, high-grade dysplasia or carcinoma). The model was validated through bootstrapping, and discrimination and calibration of the model were assessed.

RESULTS: …